DE1157627B - Process for the preparation of 5- (o-alkoxyphenoxymethyl) -oxazolidonen- (2) - Google Patents

Description

Process for the preparation of 5- (o-alkoxyphenoxymethyl) -oxazolidonenA2) The invention relates to a process for the preparation of 5- (o-alkoxyphenoxymethyl) -oxazolidonen- (2) of the general formula 1: m where K denotes a low molecular weight alkyl radical which is characterized in that, according to methods known per se, a) a 3 - (o-alkoxyphenoxy) propanol of the general formula II: in which R2 denotes a halogen atom or the hydroxyl group and R has the meaning given above, reacts with urea at elevated temperature or b) a 3- (o-alkoxyphenoxy) propanol of the general formula II, in which R2 denotes the amino group, with a Dialkyl carbonate heated in the presence of an alkali metal catalyst and an inert organic solvent until about all of the alkanol formed is distilled off, or c) a 1,2-epoxy-3-o-alkoxyphenoxypropane with urea or with sodium cyanate and hydrochloric acid or using basic Reacts catalysts with ethyl carbamate.

The implementation of 3-o-alkoxyphenoxy-1, 2-propanediol and urea can in an approximate molar ratio of 1: 2 at a temperature of about 170 to 200 ° C with ring closure.

The implementation of 3- (o-alkoxyphenoxy) -l-chloro-2-propanol and urea is carried out in a molar ratio of at least 1: 2.

Pharmacological tests have shown that the invention The compounds that can be produced are valuable relaxants for skeletal muscles.

The compounds have been shown to act as antagonists against strychnine measured. The results are shown in the table below.

At intervals of 30 or 60 and 120 minutes after the oral Administration of the substance was administered intraperitoneally to rats at 3 mg / kg of strychnine.

For each time interval, the 50% protective dose (PD,) was calculated using the method of Lichtfield and Wilcoxon. If the animals survived 3 hours, this was regarded as a sign of a protective effect. PD50 strychnine LD50 Composition 30 minutes 60 minutes 120 minutes rats oral mice oral mg / kg mg / kg mg / kg mg / kg mg / kg 5- (o-Methoxyphenoxymethyl) oxazolidone- (2) .. 135 j 175 86 1525 8 3- (o-Toloxy) -1, 2-propanediol .......... 312 - 603 625 - 3- (o-Toloxy) -2-hydroxypropyl carbamate .... 171 - 1 483 - 2.77 * 5- (o-methylphenoxymethyl) -oxazolidone- (2) .... - 420 - 773 - 2-hydroxy-3- (o-methoxyphenoxypropyl) - carbamate. ... - 393 387 1230 * Handbook of Toxicology, Vol. 1, Spector; WB Saunders Co., 1956.

From the table it can be seen that the process product is already in a lower dose has a better muscle relaxing effect than the known ones Substances.

The following examples serve to illustrate the invention.

Example 1 A mixture of 893 grams (4.5 moles) of glyceringu aajacol ether and 542 g (9.0 mol) of urea is heated to 175 to 1900C for 6 hours. then the mixture is cooled and dissolved in 1500 cm3 of 950/0 ethanol. The Ethanol The solution is filtered while it is still hot. The reaction product crystallizes out of the solution as it cools off. The crystallized product is filtered off and twice in the recrystallized from ethanol as described above.

In this way, pure 5- (o-methoxyphenoxymethyl) oxazolidone- (2) from the mp 140.5 to 142 ° C in a yield of 320 g (34 01o). The connection obtained represents a white, insoluble in water but soluble in alcohol and propylene glycol Powder.

Through further experiments, one can use acetone instead of ethanol Achieve yields between 25 and 370 / o.

Analysis for C11H13NO4: Calculated .... C 59.180 / ,, H 5.870 / 0, N 6.270 / o; found ... C 59.050 / o, H 5.81 0 / o, N 6.11 0 / o.

Example 2 A mixture of 101 g (0.47 mol) of 3- (o-methoxyphenoxy) -l-chloro-2-propanol and 168 g (2.8 mol) of urea is heated and heated at 180 to 21/2 hours 190 ° C. The reaction mixture is partitioned between water and chloroform. The chloroform extract was dried over sodium sulfate and the product with petroleum ether (Bp 65 to 110 ° C) precipitated and recrystallized from 950/0einem ethanol. the The yield is 45 g (43%).

The product obtained has a melting point of 143 to 144 "C. If the product obtained is mixed with an approximately equal amount of that according to the example 1 produced 5 - (o - methoxyphenoxymethyl) - oxazolidons- (2), then no Melting point depression of the mixture was found.

Example 3 A suspension of 46.5 g (0.236 mol) of 2-hydroxy-3- (o-methoxyphenoxy) propylamine, 27.9 g (0.236 mol) of diethyl carbonate and 250 ml of isooctane were heated under reflux. About 0.05 g of sodium metal was added immediately and after 2 and 4 hours, respectively. That Ethanol formed was distilled off from the reaction mixture. The amount of distilled Ethanol indicated that the reaction was complete in about 6 hours. The mixture was cooled and the resulting solid was recrystallized several times from 95% ethanol. The crystals had a melting point of 143 to 144 "C. A mixed melting point with the compound prepared according to Example 1, there was no lowering of the melting point.

Example 4 A mixture of 18.0 g (0.1 mol) of 1,2-epoxy-3- (o-methoxyphenoxy) propane and 12.0 g (0.2 mol) Urea was heated to 1750 ° C. The resulting exothermic The reaction was moderated by external cooling and the temperature for 2 hours was kept at 175 to 180 "C. The reaction mixture was between water and Split chloroform.

The chloroform extract was dried over sodium sulfate, filtered and focused. The remainder was purified from an ethanol 950/0 by crystallization.

The crystals had a melting point of 143 to 1450 C. A mixed melting point with the compound prepared according to Example 1, there was no lowering of the melting point.

Example 5 A mixture of 18.0 g (0.1 mol) of 1,2-epoxy-3- (o-methoxyphenoxy) propane and 17.8 g (0.2 mol) of ethyl carbamate were heated to 175 "C. 0.2 g of potassium hydroxide, dissolved in 5 mol of methanol was added.

The temperature was held at 175 to 190 "C for 2 hours. The Product was isolated as described in Example 1. The melting point of the product was 140.5 to 142 "C.

Example 6 A mixture of 18 g (0.1 mol) of 1,2-epoxy-3- (o-methoxyphenoxy) propane (a colorless oil with a range of 0.15 112 to 113 "C) and 13.0 g (0.2 mol) of sodium cyanate and 100 ml of ethanol was treated with 10 ml of concentrated hydrochloric acid, 4 hours refluxed for a long time and concentrated. The rest was between water and Split chloroform.

The chloroform extract was dried over dehydrated sodium sulfate and concentrated, the remaining oil was crystallized and extracted from 950/0 of an ethanol recrystallized. Its melting point was 143 to 145 "C.

Claims (1)

PATENT CLAIM. Process for the preparation of 5- (o-alkoxyphenoxymethyl) -oxazolidonen- (2) of the general formula I. in which R denotes a low molecular weight alkyl radical, characterized in that according to methods known per se a) a 3- (o-alkoxyphenoxy) propanol of the general formula II in which R2 denotes a halogen atom or the hydroxyl group and R has the meaning given above, reacts with urea at elevated temperature or b) a 3- (o-alkoxyphenoxy) propanol of the general formula II, in which R2 denotes the amino group, with a Dialkyl carbonate heated in the presence of an alkali metal catalyst and an inert organic solvent until about all of the alkanol formed has distilled off, or c) a 1 2-epoxy-3- (o-alkoxyphenoxypropane with urea or with sodium cyanate and hydrochloric acid or using basic catalysts with ethyl carbamate. References considered: U.S. Patent No. 2,617 825; Journ. of Pharmy and Pharmacol., IX (1957), pp. 10-19.